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Comparative Study
. 2022 Feb:150:155785.
doi: 10.1016/j.cyto.2021.155785. Epub 2021 Dec 14.

Effect of SARS-CoV-2 seropositivity on antigen - specific cytokine and chemokine responses in latent tuberculosis

Anuradha Rajamanickam  1 , Nathella Pavan Kumar  2 , Padmapriyadarsini Chandrasekaran  2 , Arul Nancy  3 , P K Bhavani  2 , Nandhini Selvaraj  3 , Kushiyasri Karunanithi  2 , Saravanan Munisankar  3 , R Srinivasan  2 , Rachel Mariam Renji  3 , Shanmuga Priya Kumaravadivelu  2 , Vijayalakshmi Venkatramani  3 , Subash Babu  3
Affiliations
Comparative Study

Effect of SARS-CoV-2 seropositivity on antigen - specific cytokine and chemokine responses in latent tuberculosis

Anuradha Rajamanickam et al. Cytokine. 2022 Feb.

Abstract

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative individuals with SARS-CoV-2 seropositivity and healthy control (both LTBI and SARS-CoV-2 negative) individuals. Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG +) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1β, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB - antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.

Keywords: Antigen specific responses; Chemokines; Cytokines; LTBI; SARS-CoV-2 seropositivity.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
LTBI+/IgG+ individualsareassociated with elevated baseline or unstimulated levels of pro-inflammatory cytokines and altered levels of anti-inflammatory cytokines. (A) The plasma levels of pro-inflammatory cytokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG+ (n = 24) and LTBI-/IgG- (n = 20) individuals at unstimulated or baseline. (B) The plasma levels of anti- inflammatory cytokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG+ (n = 24) and LTBI-/IgG- (n = 20) individuals at unstimulated or baseline. p values were calculated using the Kruskal-Wallis test with Dunn’s post-hoc for multiple comparisons.
Fig. 2
Fig. 2
LTBI+/IgG+ individualsareassociated with elevated TB antigen stimulated levels of pro-inflammatory cytokines and altered levels of anti-inflammatory cytokines. (A) The plasma levels of pro-inflammatory cytokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG+ (n = 24) and LTBI-/IgG- (n = 20) individuals upon TB antigen stimulation. (B) The plasma levels of anti- inflammatory cytokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG +(n = 24) and LTBI-/IgG- (n = 20) individuals upon TB antigen stimulation. The data are represented as scatter plots with each circle representing a single individual. p values were calculated using the Kruskal-Wallis test with Dunn’s post-hoc for multiple comparisons.
Fig. 3
Fig. 3
LTBI+/IgG+ individuals exhibit no significant differences in mitogen stimulated levels of pro and anti-inflammatory cytokines. (A) The plasma levels of pro-inflammatory cytokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n =24) individuals, LTBI-/IgG+(n = 24) and LTBI-/IgG- (n = 20) individuals upon mitogen stimulation. (B) The plasma levels of anti- inflammatory cytokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG+(n = 24) and LTBI-/IgG- (n = 20) individuals upon mitogen stimulation. The data are represented as scatter plots with each circle representing a single individual. p values were calculated using the Kruskal-Wallis test with Dunn’s post-hoc for multiple comparisons.
Fig. 4
Fig. 4
LTBI+/IgG+ individualsareassociated with elevated baseline or unstimulated levels of chemokines. The plasma levels of CC and CXC chemokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG +(n = 24) and LTBI-/IgG- (n = 20) individuals at unstimulated or baseline. The data are represented as scatter plots with each circle representing a single individual. p values were calculated using the Kruskal-Wallis test with Dunn’s post-hoc for multiple comparisons.
Fig. 5
Fig. 5
LTBI+/IgG+ individualsareassociated with elevated upon TB antigen stimulated levels of chemokines. The plasma levels of CC and CXC chemokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG+ (n = 24) and LTBI-/IgG- (n = 20) individuals upon TB antigen stimulation. The data are represented as scatter plots with each circle representing a single individual. p values were calculated using the Kruskal-Wallis test with Dunn’s post-hoc for multiple comparisons.
Fig. 6
Fig. 6
IgG+/LTBI + individuals exhibit no significant differences in mitogen stimulated levels of chemokines. The plasma levels of CC and CXC chemokines were measured in LTBI+/IgG+ (n = 35) and LTBI+/IgG- (n = 24) individuals, LTBI-/IgG+ (n = 24) and LTBI-/IgG- (n = 20) individuals upon mitogen stimulation. The data are represented as scatter plots with each circle representing a single individual. p values were calculated using the Kruskal-Wallis test with Dunn’s post-hoc for multiple comparisons.
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